Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV001017598 | SCV001178698 | likely pathogenic | Hereditary cancer-predisposing syndrome | 2019-11-06 | criteria provided, single submitter | clinical testing | The c.835-17A>G intronic variant results from an A to G substitution 17 nucleotides upstream from coding exon 8 in the APC gene. This alteration, described as 845-17A>G, has been reported in an individual from a cohort of patients with multiple-adenomatous polyps of the colorectum (Pedemonte S et al. Genes Chromosomes Cancer, 1998 Aug;22:257-67). Further, RT-PCR analysis of RNA extracted from adenomatous tissue from this patient revealed an insertion of 16 bp of intron 7, between exon 7 and 8 resulting in a premature stop codon. This nucleotide position is well conserved in available vertebrate species. Based on the majority of available evidence to date, this variant is likely to be pathogenic. |
| Fulgent Genetics, |
RCV002497341 | SCV002814011 | pathogenic | Desmoid disease, hereditary; Familial adenomatous polyposis 1; Hepatocellular carcinoma; Gastric cancer; Colorectal cancer; Gastric adenocarcinoma and proximal polyposis of the stomach | 2021-12-31 | criteria provided, single submitter | clinical testing | |
| Invitae | RCV003649202 | SCV004511665 | uncertain significance | Familial adenomatous polyposis 1 | 2023-10-16 | criteria provided, single submitter | clinical testing | This sequence change falls in intron 8 of the APC gene. It does not directly change the encoded amino acid sequence of the APC protein. This variant is not present in population databases (gnomAD no frequency). This variant has been observed in individual(s) with polyposis (PMID: 9669663). ClinVar contains an entry for this variant (Variation ID: 822326). Studies have shown that this variant is associated with altered splicing resulting in unknown protein product impact (Invitae). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |